In vivo Anti-metastatic Action of Ginseng Protopanaxadiol Saponins is Based on Their Intestinal Bacterial Metabolites After Oral Administration

다국어 초록 (Multilingual Abstract)

Ginseng(the root of Panax ginseng C. A. MEYER, Araliaceae) has been used for traditional medicine in China, Korea, Japan and other Asian countries for the treatment of various diseases including psychiatric and neurologic diseases as well as diabetes mellitus. So far, ginseng saponins(ginsenosides) have been regarded as the principal componentsresponsible for the pharmacological activities of ginseng. Previously, it was reported thatprotopanaxadiol-type ginsenisides such as Rb1, Rb2 and Rc are metabolized by intestinalbacteria after oral administration to their final derivative 20-O-b-D-glucopyranosyl-20(S)-protopanaxadiol, which is referred to as M1 or compound K. In the present study, we investigated in vivo and in vitro anti-metastatic activities of M1 in comparison with ginsenosides Rb1, Rb2 and Rc and its inhibitory mechanism of action. The main bacterial metabolite M1 is an active component of orally administered ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. M1 inhibited the proliferation of tumor cells in a time-and concentration-dependent manner, and in addition induced apoptotic cell death. The induction of apoptosis by M1 involved the up-regulation of the CDK-inhibtor p27kipl as well as the down-regulation of c-Myc and cyclic D1. The nucleosomal distribution of M1 suggests that the modification of these molecules is induced by transcriptional regulation.